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Quality specifications and their daily application to evaluate the accuracy of reference measurements for serum concentrations of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2.
Mineva, EM, Sternberg, MR, Pfeiffer, CM, Momin, SS, Maw, KL, Schleicher, RL
Clinica chimica acta; international journal of clinical chemistry. 2018;:241-249
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Abstract
BACKGROUND Reference measurement procedures (RMP) have rigorous accuracy specifications. For total 25-hydroxyvitamin D, 25(OH)D, bias ≤1.7% and CV ≤5% are recommended. These quality specifications are impractical for minor analytes, such as 25(OH)D2. Furthermore, documentation on RMP quality performance specifications for the individual 25(OH)D metabolites and their daily application are missing. METHODS To assess accuracy, we used zeta-scores. Daily, 5-10 specimens (duplicate) and 3 reference materials (singleton or duplicate) were measured for 25(OH)D3 and 25(OH)D2 using JCTLM-accepted LC-MS/MS RMPs. Protocols were repeated on 3-4 occasions to generate campaign results. We used separate zeta-score acceptability criteria for daily (≤|2|) and campaign (≤|1|) evaluations. Allowable imprecision was determined experimentally. RESULTS Across 7 campaigns, unacceptable daily zeta-scores required repeating 2 runs for 25(OH)D3 and 5 runs for 25(OH)D2. Hence, the zeta-scores of acceptable reference material results indicated high accuracy. The allowable imprecision for the RMPs was ≤5% (daily) and ≤ 3% (campaign) for 25(OH)D3 and ≤ 7% (daily) and ≤ 4% (campaign) for 25(OH)D2, respectively. CONCLUSIONS Using zeta-scores and experimentally derived imprecision, we developed a straightforward approach to assess the acceptability of individual 25(OH)D reference measurements, providing also much-needed practical accuracy specifications for 25(OH)D2.
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Parathyroid hormone, calcidiol, calcitriol and adverse events in the acute coronary syndrome.
Ramos Ruiz, P, Jaulent Huertas, L, Castañeda Sancirilo, M, Martínez Díaz, JJ, Clavel Ruipérez, G, García de Guadiana Romualdo, L, Wasniewski, S, Merelo Nicolás, M, García Escribano, I, Soria Arcos, F, et al
Medicina intensiva. 2018;(2):73-81
Abstract
OBJECTIVE To know the clinical profile as well as the prognostic significance of elevated levels of parathyroid hormone (PTH) in patients admitted for acute coronary syndrome (ACS). DESIGN AND SETTING Observational and prospective study of patients admitted for ACS in a single Spanish center during a period of six months. INTERVENTION AND VARIABLES OF INTEREST The circulating concentrations of PTH, calcidiol, calcitriol, NT-proBNP, C-reactive protein, cystatinC and fibrinogen were determined within the first 48h at admission. We performed adjusted models to predict death or re-entry for ACS after hospital discharge. RESULTS A total of 161 patients were recruited (age 67±14 years, 75.2% were men). Forty-one (25.5%) patients had elevated PTH values. During follow-up for a period of 275 person-years, 50 adverse events were recorded. Patients with elevated PTH levels were proportionally more women (21.2 vs. 39.0%) and older (63.3 vs. 77.8 years, both P<.05). Likewise, they presented significantly more cardiovascular risk and a worse prognosis during follow-up (incidence rate ratio 2.64 CI 95%: 1.5-4.6). However, in an adjusted model by the GRACE score, PTH levels were not shown to be an independent risk factor (hazard ratio=1.1; 95% CI: 0.6-2.2), neither other components of the panel. CONCLUSIONS The proportion of patients with elevated levels of PTH admitted for ACS was high. The presence of high PTH levels was associated with an unfavorable clinical profile and a worse outcome during the follow-up, although it was not an independent predictor of poor prognosis.
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Serum concentrations of interleukin 18 and 25-hydroxyvitamin D3 correlate with depression severity in men with psoriasis.
Pietrzak, D, Pietrzak, A, Grywalska, E, Kiciński, P, Roliński, J, Donica, H, Franciszkiewicz-Pietrzak, K, Borzęcki, A, Socha, M, Niedziałek, J, et al
PloS one. 2018;(8):e0201589
Abstract
OBJECTIVE Psoriasis and depression may have common mechanisms, such as systemic inflammation, dysfunction of the hypothalamic-pituitary-adrenal axis, and vitamin D3 deficiency. Among men with psoriasis, this study examined whether depression severity was associated with serum concentrations of different metabolic and inflammatory markers. METHODS The study included 85 men with psoriasis (mean age ± standard deviation [SD], 47 ± 14 years) and 65 men without psoriasis (mean age ± SD, 44 ± 13 years). In both groups, we measured the body mass index; blood pressure; and serum concentrations of lipids, uric acid, lipase, interleukins 6 and 18, cortisol, and 25-hydroxyvitamin D3. All participants completed the Beck Depression Inventory. Other variables analyzed included psoriasis duration, the Psoriasis Area Severity Index, and the percentage of body surface area affected by psoriatic lesions. RESULTS Compared with controls, patients with psoriasis had significantly greater depression severity, higher body mass indices, and higher serum concentrations of total cholesterol and interleukins 6 and 18; moreover, they had significantly lower serum 25-hydroxyvitamin D3 concentrations. In patients with psoriasis, depression severity correlated positively with psoriasis duration, the Psoriasis Area Severity Index, the percentage of body surface area affected by psoriatic lesions, and interleukin-18 concentration. In patients with psoriasis, depression severity correlated negatively with 25-hydroxyvitamin D3 concentration, but it did not correlate significantly with the serum concentrations of interleukin 6 and cortisol. CONCLUSIONS High concentrations of interleukin 18 and low concentrations of 25-hydroxyvitamin D3 may be associated with depression severity in men with psoriasis. Thus, further studies should examine whether effective anti-inflammatory treatments or vitamin D3 supplementation can improve depression outcomes in these patients.
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Treatment of non-alcoholic steatohepatitis patients with vitamin D: a double-blinded, randomized, placebo-controlled pilot study.
Geier, A, Eichinger, M, Stirnimann, G, Semela, D, Tay, F, Seifert, B, Tschopp, O, Bantel, H, Jahn, D, Marques Maggio, E, et al
Scandinavian journal of gastroenterology. 2018;(9):1114-1120
Abstract
BACKGROUND Non-alcoholic steatohepatitis (NASH) is defined by liver inflammation and consecutive fibrotic damage caused by a deposition of fat in the liver. No licensed medical treatments exist and lifestyle modification is difficult to incorporate into everyday life. We investigated the efficacy and safety of a 48-week treatment with vitamin D3 in NASH patients. METHODS Histologically determined NASH patients with elevated alanine aminotransferase (ALT) and decreased 25-OH vitamin D level at baseline received vitamin D3 or placebo orally over a 48-week period. The primary endpoint of this study was the change in ALT from baseline to the end-of-treatment. Steatohepatitis was categorized according to the Steatosis, Activity and Fibrosis Score and disease activity was assessed using the NAFLD activity score. RESULTS Serum 25-OH vitamin D levels significantly increased only in the vitamin D3 group over the 48-week treatment phase indicating compliance. In contrast to placebo, patients in the vitamin D group had markedly decreased ALT levels after the end-of-treatment phase. A significant decrease during treatment with vitamin D was also observed for cytokeratin-18 fragments compared with placebo. The study was not powered to detect changes in histological score, hence only descriptive results for histopathological characteristics are available. CONCLUSIONS Treatment with 2100 IE vitamin D q.d. over 48 weeks was well tolerated and led to a significant improvement of serum ALT levels in patients with hypovitaminosis D and histology-proven NASH as the primary endpoint together with a trend toward reduction of hepatic steatosis, which was not significant due to a small number of available biopsy specimens.
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The association between 25(OH)D levels, frailty status and obesity indices in older adults.
Sousa-Santos, AR, Afonso, C, Santos, A, Borges, N, Moreira, P, Padrão, P, Fonseca, I, Amaral, TF
PloS one. 2018;(8):e0198650
Abstract
BACKGROUND Vitamin D deficiency is common in older adults and has been linked with frailty and obesity, but it remains to be studied whether frail obese older adults are at higher risk of vitamin D deficiency. Therefore, the aim of this study is to explore the association between frailty, obesity indices and serum 25(OH)D concentrations. METHODS 1447 individuals with 65 years or older, participating in a cross-sectional study (Nutrition UP 65) were included. Frailty, according to Fried et al., body mass index (BMI), waist circumference (WC), body roundness index (BRI) and body shape index (ABSI) were evaluated. A stepwise multinomial logistic regression was carried out to quantify the association between 25(OH)D quartiles and independent variables. RESULTS Median 25(OH)D levels were lower in individuals presenting both frailty and obesity (p<0.001). In the multivariate analysis, pre-frailty (OR: 2.65; 95% CI: 1.63-4.33) and frailty (OR: 3.77; 95% CI: 2.08-6.83) were associated with increased odds of lower 25(OH)D serum levels (first quartile). Regarding obesity indices, the highest categories of BMI (OR: 1.74; 95% CI: 1.06-2.86), WC (OR: 3.46; 95% CI: 1.95-6.15), BRI (OR: 4.35; 95% CI: 2.60-7.29) and ABSI (OR: 3.17 95% CI: 1.86-5.38) were directly associated with lower 25(OH)D serum levels (first quartile). CONCLUSIONS A positive association between frailty or obesity and lower vitamin D levels was found. Moreover, besides BMI and WC, other indicators of body adiposity, such as BRI and ABSI, were associated with lower 25(OH)D serum concentrations.
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Dose-response effects of supplementation with calcifediol on serum 25-hydroxyvitamin D status and its metabolites: A randomized controlled trial in older adults.
Vaes, AMM, Tieland, M, de Regt, MF, Wittwer, J, van Loon, LJC, de Groot, LCPGM
Clinical nutrition (Edinburgh, Scotland). 2018;(3):808-814
Abstract
BACKGROUND & AIMS Oral supplementation with vitamin D is recommended for older adults to maintain a sufficient 25-hydroxyvitamin D (25(OH)D) status throughout the year. While supplementation with vitamin D2 or D3 is most common, alternative treatment regimens exist which require further investigation with respect to increasing 25(OH)D concentration. We investigated the dose-response effects of supplementation with calcifediol compared to vitamin D3 and assessed the dose which results in mean serum 25(OH)D3 concentrations between 75 and 100 nmol/L. METHODS This randomized, double-blind intervention study included men and women aged ≥65 years (n = 59). Participants received either 5, 10 or 15 μg calcifediol or 20 μg vitamin D3 per day, for a period of 24 weeks. Blood samples were collected every four weeks to assess response profiles of vitamin D related metabolites; serum vitamin D3, 25(OH)D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3). Further, serum calcium, plasma parathyroid hormone, and urinary calcium were evaluated. RESULTS Supplementation with 20 μg vitamin D3 increased 25(OH)D3 concentrations towards 70 nmol/L within 16 weeks. Supplementation with 10 or 15 μg calcifediol increased 25(OH)D3 levels >75 nmol/L in 8 and 4 weeks, respectively. Steady state was achieved from week 12 onwards with serum 25(OH)D3 levels stabilizing between 84 and 89 nmol/L in the 10 μg calcifediol group. A significant association was observed between the changes in 25(OH)D3 and 24,25(OH)2D3 (R2 = 0.83, P < 0.01), but not between 25(OH)D3 and 1,25(OH)2D3 (R2 = 0.04, P = 0.18). No cases of hypercalcemia occurred in any treatment during the study period. CONCLUSIONS Calcifediol supplementation rapidly and safely elevates serum 25(OH)D3 concentrations to improve vitamin D status in older adults. A daily dose of 10 μg calcifediol allows serum 25(OH)D3 concentrations to be maintained between 75 and 100 nmol/L. TRIAL REGISTRATION NUMBER NCT01868945.
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Comparison of the effect of daily versus bolus dose maternal vitamin D3 supplementation on the 24,25-dihydroxyvitamin D3 to 25-hydroxyvitamin D3 ratio.
Ketha, H, Thacher, TD, Oberhelman, SS, Fischer, PR, Singh, RJ, Kumar, R
Bone. 2018;:321-325
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Abstract
OBJECTIVE Supplementing lactating mothers with high doses of vitamin D3 can adequately meet vitamin D requirements of the breastfed infant. We compared the effect of bolus versus daily vitamin D3 dosing in lactating mothers on vitamin D3 catabolism. We hypothesized that catabolism of 25(OH)D3 to 24,25(OH)2D3 would be greater in the bolus than in the daily dose group. DESIGN, SETTING AND PATIENTS Randomized controlled trial (clinicaltrials.govNCT01240265) in 40 lactating women. INTERVENTIONS Subjects were randomized to receive vitamin D3 orally, either a single dose of 150,000IU or 5000IU daily for 28days. Vitamin D metabolites were measured in serum and breast milk at baseline, 1, 3, 7, 14 and 28days. MAIN OUTCOME MEASURE Temporal changes in the serum 24,25(OH)2D3/25(OH)D3 ratio. RESULTS The concentration of serum 24,25(OH)2D3 was directly related to that of 25(OH)D in both groups (r2=0.63; p<0.001). The mean (±SD) 24,25(OH)2D3/25(OH)D3 ratio remained lower at all time points than baseline values in the daily dose group (0.093±0.024, 0.084±0.025, 0.083±0.024, 0.080±0.020, 0.081±0.023, 0.083±0.018 at baseline, 1, 3, 7, 14, and 28days, respectively). In the single dose group, the increase in 24,25(OH)2D3 lagged behind that of 25(OH)D, but the 24,25(OH)2D3/25(OH)D3 values (0.098±0.032, 0.067±0.019, 0.081±0.017, 0.092±0.024, 0.103±0.020, 0.106±0.024, respectively) exceeded baseline values at 14 and 28days and were greater than the daily dose group at 14 and 28days (p=0.003). The 24,25(OH)2D3/25(OH)D3 ratio remained in the normal range with both dosing regimens. Greater breast milk vitamin D3 values in the single dose group were inversely associated with the 24,25(OH)2D3/25(OH)D3 ratio (r2=0.14, p<0.001), but not with daily dosing. CONCLUSIONS After a 14-day lag, a single high dose of vitamin D led to greater production of 24,25(OH)2D3, presumably via induction of the 24-hydroxylase enzyme (CYP24A1), relative to the 25(OH)D3 value than did daily vitamin D supplementation, and this effect persisted for at least 28days after vitamin D administration. A daily dose of vitamin D may have more lasting effectiveness in increasing 25(OH)D3 with lesser diversion of 25(OH)D3 to 24,25(OH)2D3 than does larger bolus dosing.
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The value and significance of 25(OH) and 1,25(OH) vitamin D serum levels in adult coeliac patients: A review of the literature.
Zingone, F, Ciacci, C
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2018;(8):757-760
Abstract
Within the wide spectrum of symptoms and alteration of systems that characterizes CeD, several studies indicate a low-level of vitamin D, therefore recent guidelines suggest its evaluation at the time of diagnosis. This review examines the data from existing studies in which vitamin D has been assessed in CeD patients. Our review indicates that most of the studies on vitamin D in adult CeD report a 25 (OH) vitamin D deficiency at diagnosis that disappears when the patient goes on a gluten-free diet, independently of any supplementation. Instead, when the calcitriol, the active 1,25 (OH) vitamin D form, was evaluated, it resulted in the normal range at the time of CeD diagnosis. A strict and lifelong gluten-free diet can help recover vitamin D level without any supplementation.
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Vitamin D exposure and Risk of Breast Cancer: a meta-analysis.
Estébanez, N, Gómez-Acebo, I, Palazuelos, C, Llorca, J, Dierssen-Sotos, T
Scientific reports. 2018;(1):9039
Abstract
UNLABELLED The relationship between vitamin D and breast cancer is still controversial. The present meta-analysis examines the effects of the 25(OH)D, 1,25(OH)2D and vitamin D intake on breast cancer risk. For this purpose, a PubMed, Scopus and Web of Science-databases search was conducted including all papers published with the keywords "breast cancer" and "vitamin D" with at least one reported relative risk (RR) or odds ratio (OR). In total sixty eight studies published between 1998 and 2018 were analyzed. Information about type of study, hormonal receptors and menopausal status was retrieved. Pooled OR or RR were estimated by weighting individual OR/RR by the inverse of their variance Our study showed a protective effect between 25 (OH) D and breast cancer in both cohort studies (RR = 0.85, 95%CI:0.74-0.98) and case-control studies (OR = 0.65, 95%CI: 0.56-0.76). However, analyzing by menopausal status, the protective vitamin D - breast cancer association persisted only in the premenopausal group (OR = 0.67, 95%CI: 0.49-0.92) when restricting the analysis to nested case-control studies. No significant association was found for vitamin D intake or 1,25(OH)2D. CONCLUSION This systematic review suggests a protective relationship between circulating vitamin D (measured as 25(OH) D) and breast cancer development in premenopausal women.
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Serum 25-hydroxyvitamin D3 level may be associated with olfactory dysfunction in de novo Parkinson's disease.
Kim, JE, Oh, E, Park, J, Youn, J, Kim, JS, Jang, W
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2018;:131-135
Abstract
The purpose of our study was to investigate the association between olfactory function in Parkinson's disease (PD) and serum vitamin D status. Thirty-nine patients with de novo PD were enrolled in this study. Olfactory function was assessed by an odor identification test, as a part of the KVSS (Korean version of sniffin' sticks) II test. All patients were also assessed with the NMSS (Non-Motor Symptoms Scale for PD) to check the subjective change in ability to smell. Vitamin D status was determined by measuring the level of serum 25-hydroxyvitamin D3 (25-OHD3). Multiple linear regression tests and correlation analysis were applied to verify the association between serum 25-OHD3 level and patients' subjective and objective olfactory dysfunction. The serum 25-OHD3 level was independently associated with odor identification score in patients with PD (β = 0.38, p < 0.01). Another statistically significant variable was clinical subtype of PD (Intermediate subtype: β = -0.33, p < 0.05; Akinetic rigid type: β = -0.55, p < 0.01). The serum 25-OHD3 level was also negatively correlated with the score for item number 28 in NMSS (Spearman's rho = -0.32, p < 0.05). Our results showed that vitamin D status might be an independent factor for olfactory dysfunction in PD. Although the underlying mechanism has not been clearly identified, we postulate that vitamin D plays a role in the pathogenesis of olfactory dysfunction in PD. Further investigation to elucidate the precise relationship of vitamin D to PD is essential.